Projects

Patient-specific and genome editing-engineered human iPSCs have revolutionized the field of disease modeling. iPSCs can be derived in a disease- or patient-specific context, allowing for a variety of applications: following differentiation into disease-relevant cell types, iPSCs with the desired genetic background can be used as disease models to investigate disease-causing mechanisms and to screen and test novel therapeutic compounds.

Our team offers:

• Custom generation of iPSC disease models using genome editing technology
• Access to a large biobank of iPSC lines from patients with neuronal and cardiovascular diseases
• Directed differentiation of iPSCs into disease-relevant functional cell types (including derivation of distinct neuronal or cardiac subtypes) up to organoid and tissue level
• Functional and molecular assays to assess the severity of disease-specific phenotypes, including the establishment and validation of robust readouts. 

Cell painting approaches allow the parallel recording of different cellular parameters. By using gene editing approaches to simultaneously label subcellular compartments and organelles in combination with genetic biosensors, we have taken cell painting to the next level. Our iPSC reporters enable high-content imaging-based recording of iPSC-derived cells and their response to drugs, toxins, etc. in real time over hours, days and weeks.

Our solutions include:

• Visualization of various subcellular compartments and organelles (e.g. mitochondria, endosomes, lysosomes, Golgi apparatus, nuclei, neuronal synapses, cardiac sarcomeres, etc.)
• Development and optimization of genetic biosensors (e.g. for recording apoptosis or activity of distinct signaling pathways)

Human iPSCs and disease-relevant iPSC-derived cell types (such as neurons, hepatocytes or cardiomyocytes) are a powerful tool for testing cellular responses to substances, drugs and toxins to identify novel therapeutics or toxic doses of agents. Here, automated high-content imaging systems combined with AI-assisted deep learning approaches enable the simultaneous screening of multiple compounds and the detection of unbiased and unpredictable phenotypic patterns.

Our solutions include:

• Establishment and optimization of disease-specific iPSC-based screening platforms for real-time drug and toxicity testing
• Use of iPSC disease models and cell painting 2.0 iPSC reporters in high-content screening platforms

Fell J, Pavez-Giani MG, Koitka F, Kensah G, Santos GL, van der Vorst EPC, Lenz C, Salinas G, Busley AV, Fedorenko A, Hindmarsh R, Wolf CM, Lutz S, Hasenfuss G, Zimmermann WH, Wollnik B, Cyganek L. Targeting Interleukin-8-Mediated Cellular Crosstalk Reverses Hypertrophic Cardiomyopathy and Cardiac Fibrosis in Noonan Syndrome.
Circulation. 2026.
doi: 10.1161/CIRCULATIONAHA.125.074155

Zink A, Dai DF, Wittich A, Henke MT, Pedrotti G, Heiduschka S, Aguilar GS, Pentimalli TM, Brueser C, Notopoulou S, Zhaivoron A, Umar AR, Petersilie L, Jerred C, Bergmans J, Schumacher F, Keller-Findeisen J, Rybak-Wolf A, Stach D, Reinshagen J, Zaliani A, Haferkamp U, Euro L, Di Donfrancesco A, Santanatoglia C, Cappellozza E, Suarez Cubero M, Pavez-Giani M, Bakumenko O, Meierhofer D, Foley A, Morales-Gonzalez S, Tolle I, Herebian D, Bonesso D, Szabo I, Cecchetto G, Wong S, Moresco M, Maresca A, Decimo I, Adjobo-Hermans MJW, Kleuser B, Cyganek L, Mühlhausen C, Schlotawa L, Tiranti V, Rossi A, Mayatepek E, La Morgia C, Carelli V, Klopstock T, Distelmaier F, Ullah G, Jakobs S, Rajewsky N, Rose CR, Petrakis S, Edenhofer F, Koopmann W, Brunetti D, Lisowski P, Suomalainen A, del Sol A, Bottani E, Pless O, Schuelke M, Prigione A. Pluripotent stem cell-based drug discovery uncovers sildenafil as a treatment for mitochondrial disease.
Cell. 2026; 189(6):1656-1679.e42.
doi: 10.1016/j.cell.2026.02.008.

Alekseev A, Hunniford V, Zerche M, Jeschke M, El May F, Vavakou A, Siegenthaler D, Hüser MA, Kiehn SM, Garrido-Charles A, Meyer A, Rambousky A, Alvanos T, Witzke I, Rojas-Garcia KD, Draband MD, Cyganek L, Klein E, Ruther P, Huet A, Trenholm S, Macé E, Kusch K, Bruegmann T, Wolf BJ, Mager T, Moser T. Efficient and sustained optogenetic control of sensory and cardiac systems.
Nat Biomed Eng. 2025;
doi: 10.1038/s41551-025-01461-1

Bögershausen N, Cavdarli B, Nagai TH, Milev MP, Wolff A, Mehranfar M, Schmidt J, Choudhary D, Gutiérrez-Gutiérrez Ó, Cyganek L, Saint-Dic D, Zibat A, Köhrer K, Wollenweber TE, Wieczorek D, Altmüller J, Borodina T, Kaçar D, Haliloğlu G, Li Y, Thiel C, Sacher M, Knapik EW, Yigit G, Wollnik B. SEC24C deficiency causes trafficking and glycosylation abnormalities in an epileptic encephalopathy with cataracts and dyserythropoeisis.
JCI Insight. 2025; 10(9):e173484.
doi: 10.1172/jci.insight.173484

Busley AV, Gutiérrez-Gutiérrez Ó, Hammer E, Koitka F, Mirzaiebadizi A, Steinegger M, Pape C, Böhmer L, Schroeder H, Kleinsorge M, Engler M, Cirstea IC, Gremer L, Willbold D, Altmüller J, Marbach F, Hasenfuss G, Zimmermann WH, Ahmadian MR, Wollnik B, Cyganek L. Mutation-induced LZTR1 polymerization provokes cardiac pathology in recessive Noonan syndrome.
Cell Rep. 2024; 43(7):114448.
doi: 10.1016/j.celrep.2024.114448

Knauer C, Haltern H, Schoger E, Kügler S, Roos L, Zelarayán LC, Hasenfuss G, Zimmermann WH, Wollnik B, Cyganek L. Preclinical evaluation of CRISPR-based therapies for Noonan syndrome caused by deep-intronic LZTR1 variants.
Mol Ther Nucleic Acids. 2024; 35(1):102123.
doi: 10.1016/j.omtn.2024.102123